1. Field of the Invention
This invention relates to electrodes for use in measuring hydrogen ion concentration that use antimony as the electrode's sensing element, and in particular it relates to pH electrodes for measuring acidity in stomach fluids.
2. History of The Invention
The present invention involves a solid state electrochemically ion-selective electrode system preferably for measuring the pH of solutions, especially stomach fluids, and it relates to using untreated graphite and a pH sensing material (graphite/metal) as a novel internal reference electrode system.
There is a long-felt need in the health care industry for a relatively inexpensive and yet stable electrode for accurately measuring the hydrogen ion concentration, or pH, of stomach secretions. This is especially relevant in the care of acutely ill or traumatized patients who frequently die from bleeding gastric ulcers produced by stress. These ulcers are the result of an abnormally high concentration of hydrogen ions in the stomach fluid, and may be diagnosed from the presence of a low pH. Such patients' stomach pH should therefore be monitored continuously over a period of several days in order that their ulcers may be controlled by effective medication. Unfortunately, such monitoring has not heretofore been practical due to the pH electrodes that have been available. An electrode to effectively meet patient needs should: be small and flexible enough to be inserted with minimal patient discomfort; give a stable pH reading over a period of three to four days; and be inexpensive to construct. A need for such an electrode is clearly demonstrated from an examination of current methods of bleeding ulcer treatment.
Ulcer treatment has generally been based on raising the pH of the stomach fluids through the use of antacids. Antacids are administered when stomach fluid samples, taken periodically, become too acidic.
There are currently three methods of measuring gastric pH:
(1) Electrochemically by a pH electrode placed in aspirated stomach fluid; PA1 (2) Visual color matching of litmus paper, exposed to aspirated stomach fluid; PA1 (3) Electrochemically by an indwelling stomach pH electrode.
The first two techniques do not provide instant information or "real-time" data for the physician, as they must be taken after the stomach fluid has been removed and are costly due to the labor involved in acquiring a fresh sample of stomach fluid for each measurement.
An alternative to frequent stomach fluid sampling has been to administer cimetidine, a substance which prevents the histamine induced release of acid into the stomach as set out in R. Herrmann and D. L. Kaminski, "Evaluation of Intragastic pH in Acutely Ill Patients", Arch. Surg. 14, 511-514, 1979. Currently in such treatment, there is no satisfactory method of monitoring pH which will give physicians immediate data on the patient's response to the cimetidine. Cimetidine is admistered until there is an indication from periodic stomach samples that bleeding has stopped. As a result, the patient may be receiving insufficient or excess amounts of cimetidine. One problem with this line of treatment is that there is insufficient experimental evidence available to describe possible side-effects from over-administration of cimetidine. Finally, the cost of administering cimetidine is currently about twice as high as conventional antacid treatment, and therefore determination of minimum effective levels through immediate response monitoring as is provided by the present invention would benefit the cost of patient care as well as preventing possibly unknown side-effects.
A third method of monitoring gastric fluid pH is direct measurement with an indwelling pH electrode that will give the physician an immediate accurate reading of pH values. With this procedure, various modes of treatments can be assessed rapidly and safe dosage levels can be established with accuracy. Two main types of indwelling pH electrodes that are currently in use are constructed of either glass or antimony. Current glass pH electrodes appropriate for gastric analysis, are fragile and expensive to produce and transport. Such electrodes exhibit a high electrical resistance resulting in a protracted time response. A general discussion of some earlier antimony electrodes for measuring the acidity of stomach secretions is set out in: Erb, R. C., and Senior, K. L.: J. Am. Osteopath. Assoc. 38, 95, 1938; and Haggard, H. W., and Greenberg, L. A.: Science 93, 479, 1941.
3. Prior Art:
The use of an antimony electrode as a pH sensor was first reported in 1923, A. Uhl and W. Krestanek, "Die Elektrometrische Titration Vonsauren and Basen mit der Antimon-indikatorelektrode", Sitzungsberichte d. mathem.-naturw. dl., Abt. IIb, 132, 29, 1923. As set out therefore, electrodes were made of an antimony sensor connected directly to a copper wire, and the electrode was enclosed in a glass tube except for the exposed antimony sensor. This basic design has been reviewed in J. T. Stock, W. C. Purdy and L. M. Garcia, "The Antimony-Antimony Oxide Electrode", Chem. Rev. 58, 611-626, 1958. These electrodes remained essentially unchanged for a considerable time despite their inherent instability. A microelectrode version thereof has been described in, G. Malnic and F. L. Vieira, "The Antimony Microelectrode in Kidney Micropuncture", Yale J. Biol. Med. 45, 356-367, 1972.
More recently, several improvements in antimony electrodes have been reported that yield more stable results. One such electrode involves an antimony microelectrode that utilizes a silver/silver chloride internal reference system that was described in H. I. Bicher and S. Ohki, "Intracellular pH Electrode Experiments on the Giant Squid Axon" Biochim. Biophys. Acta 255, 900-904, 1972. This electrode consists of a glass tube containing an exposed antimony electrochemically connected to a silver/silver chloride wire by a solution of potassium chloride.
I. Kleinberg in, "Antimony electrodes and Methods of Manufacturing Same," U.S. Pat. No. 3,742,594, 1973, sets out the importance of using epoxy instead of glass to electrically insulate an antimony sensor from an electrical lead. The patent recognizes the antimony contains micro crevices, and these crevices are though to produce channels for water and electrolytes and thereby short-circuit the electrical potential changes that are due to a change in pH. Therein, the use of a silver wire between the antimony and a copper electrical lead was stressed, but its importance as a standard internal reference system was not described. Whereas, the present invention utilizes untreated graphite both as the conductor and as the internal reference at the junction of that graphite to an antimony sensor. In addition, production of the Kleinburg electrode requires precision soldering of the antimony micro-rods to a silver wire.
Recently it was determined that the design of Kleinberg could be further improved by using elaborately prepared single crystals of antimony or monocrystalline antimony, N. E. G. Edwall and G. S. Eklund "Monocrystalline Metal Electrode and Method of Use", U. S. Pat. No. 4,119,498; 1978. Production of this Edwall electrode however requires extremely precise measurements and manipulations of monocrystalline antimony, and minor flaws in the antimony crystal structure will cause the electrode to inaccurately sense changes in pH. Such electrode is therefore very labor intensive and is extremely expensive to produce.
The accuracy and stability of antimony electrodes generally has been attributed to the stability of a defined internal reference system that involves a reversible electrochemical system based on well established reduction-oxidation principles. Such has been detailed in, J. Ruzicka and C. G. Lamm, "Electrode for Potentiometric Measurements", U.S. Pat. No. 3,926,765; 1975. This patent teaches an electrochemically active redox system that is sensitive to ions in solution, and a humid, solid, water soluble compound which acts as a carrier for this redox system. The importance of this internal reference system was demonstrated in Kleinberg by a substitution of a silver for a copper wire, which substitutuion resulted in an extremely stable electrode.
Antimony pH electrodes that utilize a standard internal reference system are commercially available. One such antimony pH electrode is marketed by Diamond Electro-Tech Inc., (Ann Arbor, MI) and is available in either a miniature tip size (1 mm diameter) or a micro tip size (80 .mu.m diameter). Unlike the present invention, each of these electrodes use a silver wire as the standard internal reference electrode system. Another antimony pH electrode is commercially available from Harco Electronic, Ltd. (Winnipeg, Manitoba, Canada). This electrode also utilizes silver as the inernal reference system and includes epoxy to seal the micro crevices between a plastic sheath and the antimony that is similar to the electrode taught in, I. Kleinberg, "Antimony electrodes and Methods of Manufacturing Same", U.S. Pat. No. 3,742,594; 1973.
Where other pH electrodes have used materials other than antimony for the pH sensor, such have consistantly taught the use of silver as the material of a standard internal reference junction therewith. For example, the metal palladium (Pd) will respond to pH changes and has been used as an electrode sensor element. Such palladium electrodes have used an internal reference junction made of silver. This is set out in, R. L. Coon, N. C. J. Lai and J. P. Kampine, "Evaluation of a Dual-Function pH and pCO.sub.2 In-Vivo Sensor", J. Appl. Physiol. 40: 625-629, 1976. Another type of pH sensor that includes a non-metal embedded in plastic and uses silver as the internal reference system is set out in, O. H. LeBlanc, Jr., J. F. Brown, Jr., J. F. Klebe, L. W. Niedrach, G. M. J. Sluxarczuk and W. H. Stoddard, Jr., "Polymer Membrane Sensors for Continuous Intravascular Monitoring of Blood pH", J. Appl. Physiol. 40, 644-647, 1976. A more recent reference that teaches a use of silver in conjunction with one of its salts or the reduced metal salt (e.g. silver black) to produce a stable electrode system is set out in, J. A. R. Kater, "Ion-Selective Electrodes", U.S. Pat. No. 4,340,457; 1982. This patent teaches adding silver black and platinum black to a standard internal reference system, like that set out in Ruzicka, and is employed in order toenhance electrode stability.
An exception to the above wherein is taught a use of a well-defined standard internal reference electrode system is shown in FIG. 5 of a patent by, I. Binder and H. A. Teass, Jr., "An All Solid State Electrode System", U.S. Pat. No. 4,338,175; 1982. It is, however, not possible to evaluate the preferred internal reference system from the description given in this patent. Unlike the present invention however, the electrode system of this patent is configured for use in mining and mineral processing and the electrode system itself is contructed of two electrodes; one made of a noble metal that functions as the reference electrode, with the other made of ultra-pure antimony that is sensitive to fluctuations in ion levels in a solution whose ph is to be measured. This electrode is very expensive to construct as the antimony must be ultra-pure (99.999% antimony), as a less pure grade will not give stable and reproducible pH readings. Application of this arrangement as an indwelling pH electrode is therefore not practical due to its complexity and its use of expensive metals.
The present inventors have used graphite in an ion-sensitive electrode as an internal reference system when that graphite is appropriately chemically treated with a coating of a silanizing agent, H. M. Brown, Jr. and J. D. Owen, "Solid State Graphite Electrode", U.S. Pat. No. 4,431,508; 1984. This patent, however, does not teach, as does the present invention that graphite which has not been chemically or physically altered will form a stable internal reference system when coupled with a metal pH sensor, that is preferably an antimony/antimony oxide section.
The present invention differs from the above-cited references and patents, as set out above, in a number of significant ways. It does not require a labor-intensive mono-crystalline antimony manipulation. Instead its practice can involve a number of different forms of polycrystalline antimony that are easily mixed together and are preferably joined either during or after that mixing process to a body formed of untreated graphite fibers that are joined in a bundle, the graphite at the junction functioning as an internal reference system. The electrode of the present invention, therefore, does not require a use of silver for either connection between an antimony sensor and an electrical lead, as do a number of the earlier electrodes. The electrode of the present invention can be used conveniently in conjunction with a standard potentiometer and a standard electrocardiogram (E.K.G.) lead which forms the external reference electrode. The electrodes can be designed for minimal patient discomfort, are inexpensive to construct, and are disposable. Also, the electrode of the present invention requires no pre-calibration, thereby reducing labor costs associated with measuring stomach fluid pH, making it far less expensive to produce and to use than earlier antimony electrodes.